Advances in the treatment of malignant ascites in China.

PURPOSE: Malignant ascites (MA) often occurs in recurrent abdominal malignant tumors, and the large amount of ascites associated with cancerous peritonitis not only leads to severe abdominal distension and breathing difficulties, but also reduces the patient's quality of life and ability to resist diseases, which usually makes it difficult to carry out anti-cancer treatment. The exploration of MA treatment methods is also a key link in MA treatment. This article is going to review the treatment of MA, to provide details for further research on the treatment of MA, and to provide some guidance for the clinical treatment of MA. METHOD: This review analyzes various expert papers and summarizes them to obtain the paper. RESULT: There are various treatment methods for MA, including systemic therapy and local therapy. Among them, systemic therapy includes diuretic therapy, chemotherapy, immunotherapy, targeted therapy, anti angiogenic therapy, CAR-T, and vaccine. Local therapy includes puncture surgery, peritoneal vein shunt surgery, acellular ascites infusion therapy, radioactive nuclide intraperitoneal injection therapy, tunnel catheter, and intraperitoneal hyperthermia chemotherapy. And traditional Chinese medicine treatment has also played a role in enhancing efficacy and reducing toxicity to a certain extent. CONCLUSION: Although there has been significant progress in the treatment of MA, it is still one of the clinical difficulties. Exploring the combination or method of drugs with the best therapeutic effect and the least adverse reactions to control MA is still an urgent problem to be solved.

THUMPD3-TRMT112 is a m2G methyltransferase working on a broad range of tRNA substrates.

Post-transcriptional modifications affect tRNA biology and are closely associated with human diseases. However, progress on the functional analysis of tRNA modifications in metazoans has been slow because of the difficulty in identifying modifying enzymes. For example, the biogenesis and function of the prevalent N2-methylguanosine (m2G) at the sixth position of tRNAs in eukaryotes has long remained enigmatic. Herein, using a reverse genetics approach coupled with RNA-mass spectrometry, we identified that THUMP domain-containing protein 3 (THUMPD3) is responsible for tRNA: m2G6 formation in human cells. However, THUMPD3 alone could not modify tRNAs. Instead, multifunctional methyltransferase subunit TRM112-like protein (TRMT112) interacts with THUMPD3 to activate its methyltransferase activity. In the in vitro enzymatic assay system, THUMPD3-TRMT112 could methylate all the 26 tested G6-containing human cytoplasmic tRNAs by recognizing the characteristic 3'-CCA of mature tRNAs. We also showed that m2G7 of tRNATrp was introduced by THUMPD3-TRMT112. Furthermore, THUMPD3 is widely expressed in mouse tissues, with an extremely high level in the testis. THUMPD3-knockout cells exhibited impaired global protein synthesis and reduced growth. Our data highlight the significance of the tRNA: m2G6/7 modification and pave a way for further studies of the role of m2G in sperm tRNA derived fragments.

Supraphysiological estradiol promotes human T follicular helper cell differentiation and favours humoural immunity during in vitro fertilization.

During pregnancy, humoural immunity is essential for protection against many extracellular pathogens; however, autoimmune diseases may be induced or aggravated. T follicular helper (Tfh) cells contribute to humoural immunity. The aim of this study was to test whether Tfh cell function can be manipulated via hormones. Seventy-four women who underwent in vitro fertilization were recruited and divided into four groups: menstrual period (MP), controlled ovarian hyperstimulation (COH), embryo transfer (ET) and pregnant after embryo transfer (P). A flow cytometry analysis was performed to identify Tfh cells in peripheral blood mononuclear cells (PBMCs). Bioinformatics analysis revealed a possible pathway between Tfh and B cells. Enzyme-linked immunosorbent assays were used to detect interleukin (IL)-21 and IL-6. The quantitative polymerase chain reaction was performed to quantify BCL-6, BACH2, XBP-1, IRF-4 and G protein-coupled (GP)ER-1 mRNA expression. Compared with the MP group, the COH, ET and P groups showed more Tfh and B cells, as well as higher IL-21, IL-6, BCL-6 and BACH2 expression. Furthermore, Tfh cell frequency in PBMCs, as well as serum IL-21 and IL-6 levels, were all positively correlated with serum estradiol (E2 ) levels; the B cell percentage also correlated positively with Tfh cells in PBMCs. Combined with the bioinformatics analysis, XBP-1, IRF-4 and GPER-1 expression was related to E2 levels, both in vivo and in vitro. We speculate that E2 augments Tfh cells and favours humoural immunity. This study indicates that Tfh cell regulation may be a novel target in maintaining the maternal-foetal immune balance.

Micro-flow hydrophilic interaction liquid chromatography coupled with triple quadrupole mass spectrometry detects modified nucleosides in the transfer RNA pool of cyanobacteria.

Post-transcriptional modification of nucleosides is observed in almost all elements of RNA. Modified nucleosides finely tune the structure of RNA molecules and affect vital functions, such as the modified wobble position 34 of transfer RNAs expanding the reading preference of anticodons to codons. Recent investigations have revealed that the modification species and their frequencies in an RNA element are not stable but vary with specific cellular factors including metabolites and particular proteins (writers, readers, and erasers). To understand the link between dynamic RNA modifications and biological processes, sensitive and reliable methods for determining modified nucleosides are required. In this study, micro-flow (8 µL/min) hydrophilic interaction liquid chromatography was coupled with triple quadrupole mass spectrometry for the simultaneous determination of adenosine, uridine, cytidine, guanosine, and 20 modified nucleosides. The method was calibrated using 0.1-1000 nM standards (∼0.03-300 ng/mL) and successfully applied to the determination of transfer RNA modifications in the model cyanobacterium Synechococcus elongatus PCC 7942. A protocol for the isolation of a clean transfer RNA pool was optimized, requiring only 25 ng for the identification and quantification of transfer RNA modifications. This micro-flow liquid chromatography-tandem mass spectrometry method constitutes the first step toward monitoring dynamic ribonucleoside modifications in a limited RNA sample.

Zinc is essential for the transcription function of the PGC-1α/Nrf2 signaling pathway in human primary endometrial stromal cells.

Zinc (Zn) has antioxidant effect in different types of organs and is closely associated with human health. Endometrial receptivity is one of the most important factors in the embryo implantation and development. However, the regulatory mechanism of Zn in endometrium tissue is still unclear. In the study, we found that plasma Zn level is significantly associated with female infertility, which severely affects female reproductive health. Primary endometrial stromal cells were isolated from female endometrium and cultured in the laboratory. Zn chelator TPEN treatment reduced the expression of stem cell markers CD73, CD90, and CD105 and generated reactive oxygen species in endometrial stromal cells. However, pretreatment of Zn (zinc sulfate) is able to prevent TPEN-induced oxidative stress in vitro. By transcriptional profiling and gene ontology analysis, we found that Zn increased the cellular pluripotency signaling and extracellular matrix-receptor interaction, but reduced autophagy, endocytosis, and the nitrogen metabolism pathway. We further discovered the antioxidant function of Zn through the peroxisome proliferator-activated receptor gamma coactivator 1α/nuclear factor erythroid-2-related factor signaling pathway in endometrial stromal cells. Zn supplementation may open up an effective therapeutic approach for patients with oxidative stress-related endometrial diseases.

Reduced risk of dyslipidaemia with oolong tea consumption: a population-based study in southern China.

Experimental studies have suggested that tea consumption could lower the risk of dyslipidaemia. However, epidemiological evidence is limited, especially in southern China, where oolong tea is the most widely consumed beverage. We conducted a population-based case-control study to evaluate the association between consumption of tea, especially oolong tea, and risk of dyslipidaemia in Shantou, southern China, from 2010 to 2011. Information on tea consumption, lifestyle characteristics and food consumption frequency of 1651 patients with newly diagnosed dyslipidaemia and 1390 controls was obtained using a semi-quantitative questionnaire. Anthropometric variables and serum biochemical indices were determined. Drinking more than 600 ml (2 paos) of green, oolong or black tea daily was found to be associated with the lowest odds of dyslipidaemia risk (P< 0.001) when compared with non-consumption, but only oolong tea consumption was found to be associated with low HDL-cholesterol levels. A dose-response relationship between duration of tea consumption and risk of dyslipidaemia (OR 0.10, 95% CI 0.06, 0.16), as well as that between amount of dried tea leaves brewed and risk of dyslipidaemia (OR 0.34, 95% CI 0.24, 0.48), was found. Moreover, consumption of oolong tea for the longest duration was found to be associated with 3.22, 11.99 and 6.69% lower blood total cholesterol, TAG and LDL-cholesterol levels, respectively. In conclusion, the present study indicates that long-term oolong tea consumption may be associated with a lower risk of dyslipidaemia in the population of Shantou in southern China.

Whispers of the polycystic ovary syndrome theater: Directing role of long noncoding RNAs.

Polycystic Ovary Syndrome (PCOS) is a multifaceted endocrine disorder that implicates a spectrum of clinical manifestations, including hormonal imbalance, metabolic dysfunction, and even compromised ovarian granulosa cell (GC) activity. The underlying molecular mechanisms of PCOS remain elusive, presenting a significant barrier to effective diagnosis and treatment. This review delves into the emerging role of long non-coding RNAs (lncRNAs) in the pathophysiology of PCOS, articulating their intricate interactions with mRNAs, microRNAs, and other epigenetic regulators that collectively influence the hormonal and metabolic milieu of PCOS. We examine the dynamic regulatory networks orchestrated by lncRNAs that impact GC function, steroidogenesis, insulin resistance, and inflammatory pathways. By integrating findings from recent studies, we illuminate the potential of lncRNAs as biomarkers for PCOS and highlight their contribution to the disorder, offering a detailed perspective on the lncRNA-mediated modulation of gene expression and pathogenic pathways. Understanding targeted lncRNA interactions with PCOS proposes novel avenues for therapeutic intervention to ameliorate the reproductive and metabolic disturbances characteristic of the syndrome.

Asiatic acid inhibits cervical cancer cell proliferation and migration via PI3K/AKT/mTOR signaling pathway.

Cervical cancer (CC) is a malignant tumor of the female reproductive system that typically occurs in cervical cells and has high incidence and mortality rates, strong metastatic ability, and poor prognosis. Asiatic acid (AA) exhibits anti-inflammatory, anti-depressant, and anti-tumor effects. However, the molecular targets and mechanisms underlying AA-mediated inhibition of CC metastasis remain unclear. AA affects the proliferation, metastasis, and epithelial-mesenchymal transition (EMT) process of CC cell lines. MTT experiments verified that AA inhibited the proliferation ability of CC cells, and the effect of AA on the lateral and longitudinal migration ability of CC was evaluated through wound healing and Transwell assays. Western blotting was used to explore whether AA inhibits EMT process in HeLa and C33a cells. Currently, targeting the PI3K/AKT/mTOR pathway as a strategy for cancer treatment remains an evolving field. However, the molecular mechanism by which AA inhibits CC via the PI3K/AKT/mTOR pathway remains unclear and requires further investigation.

Intrauterine injection of bioengineered hydrogel loaded exosomes derived from HUCM stem cells and spermidine prominently augments the pregnancy rate in thin endometrium rats.

The endometrium is essential to the development of embryos and pregnancy. Human umbilical cord mesenchymal stem cells (HUCMSCs) are promising stem cell sources. HUCMSCs self-renew quickly and are painless to collect. Spermidine is an inherent polyamine needed for cellular and molecular processes that regulate physiology and function. HUCMSCs and spermidine (SN) may heal intrauterine adhesions. HUCMSCs were investigated for endometrial repair in rats. Composite hydrogels are used for medical exosome implantation, including their materials, properties, and embedding procedures. This study examined whether bioengineered hydrogel-loaded exosomes from HUCMSCs and spermidine prenatally improved conception rates in mice with poor endometrial lining. The data show that HUCMSC and SN provide a good experimental base for HUCMSC safety and intrauterine treatment in rats. Western blots, exosome structural analysis, pregnancy outcomes, flow cytometry, H&E staining, immunohistochemistry, and immunofluorescence labelling found and recovered the aberrant area. HUCM-derived stem cells and spermidine-derived exosomes biophysically match. These traits strengthen and prolong endometrial function. Pregnant rats with HUCMSC and SN had thinner endometrium. Hydrogel-incorporated HEHUCMSC and SN exosomes may improve IUI in rats with thin endometrium.

Clinical characteristics and prognosis of pancreatitis associated with immune checkpoint inhibitors.

BACKGROUND AND OBJECTIVE: Immune checkpoint inhibitors (ICIs) have shown remarkable efficacy against various cancers in clinical practice. However, ICIs can cause immune checkpoint inhibitor-associated pancreatic injury, often leading to drug withdrawal, and then patients must go to specialized treatment. The patients, their primary tumors are sensitive to ICIs therapy, may experience treatment delays due to such adverse reactions. Therefore, there is a need for systematic clinical researches on immune-related pancreatic toxicity to provide a clinical basis for its prevention and treatment. METHODS: This study involved the collection of data from patients treated with ICIs and addressed pancreatic injury with preemptive treatment before continuing ICIs therapy. Then, we also statistically analyzed the incidence of pancreatic injury in patients with different courses and combined treatment, and the success rate of rechallenge treatment. RESULTS: The study included 62 patients, with 33.9% (21/62) experiencing varying degrees of pancreatic injury. Patients with pancreatic injury, 10 cases evolved into pancreatitis, representing 47.6% (10/21) in the pancreatic injury subgroup and 16.1% (10/62) of the total patient cohort. Preemptive treatment was administered to 47.6% (10/21) of patients with pancreatitis, the effective rate was 100%. Among these patients, 70% (7/10) underwent successful rechallenge with ICIs. The occurrence of pancreatic injury was positively correlated with the treatment duration (P < 0.05) but showed no significant correlation with combination therapies (P > 0.05). CONCLUSION: The likelihood of pancreatic injury increased with longer treatment durations with ICIs; no significant association was found between the incidence of ICIs-related pancreatic damage and combination therapies. Preemptive treatment for immune-related pancreatitis is feasible, allowing some patients to successfully undergo rechallenge with ICIs therapy.

The engineering of defect-modified boron nitride ribbons: an effective adsorbent to rapid capture for tetracycline.

Antibiotics, the persistent organic pollutants, have brought serious pollution to the aquatic environment. Therefore, it is necessary to select rapid adsorbents to remove them from their long-term threat. Herein, the introduction of defects in BN was employed to enhance its surface chemical activity for rapid capture of tetracycline via hydrothermal and calcination methods. The defect content in BN can be controlled by adjusting the volume ratio of ethanol to water. Among them, when the volume ratio of H2O/ethanol is 4/1 (BN-3), BN-3 has the most N defects at 33%, which increases the adsorption rate of h-BN for TC and promotes the adsorption capacity to 302.15 mg g-1, which is due to the introduction of nitrogen defects significantly regulates the electronic structure of BN. The corresponding theoretical calculations confirm that BN with N defects decreases the absorption energy of BN for TC. Additionally, the adsorption removal rate of tetracycline still reached 95.5% after 5 cycles of TC adsorption by BN-3, indicating that the defect-modified BN has good reusability and is beneficial for its use in pollutant adsorption.

Hierarchical antibiotic delivery system based on calcium phosphate cement/montmorillonite-gentamicin sulfate with drug release pathways.

Antibiotic-loaded calcium phosphate cement (CPC) has emerged as a promising biomaterial for drug delivery in orthopedics. However, there are problems such as the burst release of antibiotics, low cumulative release ratio, inappropriate release cycle, inferior mechanical strength, and poor anti-collapse properties. In this research, montmorillonite-gentamicin (MMT-GS) was fabricated by solution intercalation method and served as the drug release pathways in CPC to avoid burst release of GS, achieving promoted cumulative release ratios and a release cycle matched the time of inflammatory response. The results indicated that the highest cumulative release ratio and release concentration of GS in CPC/MMT-GS was 94.1 ± 2.8 % and 1183.05 µg/mL, and the release cycle was up to 504 h. In addition, the hierarchical GS delivery system was divided into three stages, and the kinetics followed the Korsmeyer-Peppas model, the zero-order model, and the diffusion-dissolution model, respectively. Meanwhile, the compressive strength of CPC/MMT-GS was up to 51.33 ± 3.62 MPa. Antibacterial results demonstrated that CPC/MMT-GS exhibited excellent in vitro long-lasting antibacterial properties to E. coli and S. aureus. Furthermore, CPC/MMT-GS promoted osteoblast proliferation and exhibited excellent in vivo histocompatibility. Therefore, CPC/MMT-GS has favorable application prospects in the treatment of bone defects with bacterial infections and inflammatory reactions.

A Preliminary Survey of Transfer RNA Modifications and Modifying Enzymes of the Tropical Plant Cocos nucifera L.

The coconut (Cocos nucifera L.) is a commercial crop widely distributed among coastal tropical regions. It provides millions of farmers with food, fuel, cosmetics, folk medicine, and building materials. Among these, oil and palm sugar are representative extracts. However, this unique living species of Cocos has only been preliminarily studied at molecular levels. Benefiting from the genomic sequence data published in 2017 and 2021, we investigated the transfer RNA (tRNA) modifications and modifying enzymes of the coconut in this survey. An extraction method for the tRNA pool from coconut flesh was built. In total, 33 species of modified nucleosides and 66 homologous genes of modifying enzymes were confirmed using a nucleoside analysis using high-performance liquid chromatography combined with high-resolution mass spectrometry (HPLC-HRMS) and homologous protein sequence alignment. The positions of tRNA modifications, including pseudouridines, were preliminarily mapped using a oligonucleotide analysis, and the features of their modifying enzymes were summarized. Interestingly, we found that the gene encoding the modifying enzyme of 2'-O-ribosyladenosine at the 64th position of tRNA (Ar(p)64) was uniquely overexpressed under high-salinity stress. In contrast, most other tRNA-modifying enzymes were downregulated with mining transcriptomic sequencing data. According to previous physiological studies of Ar(p)64, the coconut appears to enhance the quality control of the translation process when subjected to high-salinity stress. We hope this survey can help advance research on tRNA modification and scientific studies of the coconut, as well as thinking of the safety and nutritional value of naturally modified nucleosides.

Mitochondrial RNA m3C methyltransferase METTL8 relies on an isoform-specific N-terminal extension and modifies multiple heterogenous tRNAs.

Methyltransferase-like 8 (METTL8) encodes a mitochondria-localized METTL8-Iso1 and a nucleolus-distributed METTL8-Iso4 isoform, which differ only in their N-terminal extension (N-extension), by mRNA alternative splicing. METTL8-Iso1 generates 3-methylcytidine at position 32 (m3C32) of mitochondrial tRNAThr and tRNASer(UCN). Whether METTL8-Iso4 is an active m3C32 methyltransferase and the role of the N-extension in mitochondrial tRNA m3C32 formation remain unclear. Here, we revealed that METTL8-Iso4 was inactive in m3C32 generation due to the lack of N-extension, which contains several absolutely conserved modification-critical residues; the counterparts were likewise essential in cytoplasmic m3C32 biogenesis by methyltransferase-like 2A (METTL2A) or budding yeasts tRNA N3-methylcytidine methyltransferase (Trm140), in vitro and in vivo. Cross-compartment/species tRNA modification assays unexpectedly found that METTL8-Iso1 efficiently introduced m3C32 to several cytoplasmic or even bacterial tRNAs in vitro. m3C32 did not influence tRNAThrN6-threonylcarbamoyladenosine (t6A) modification or aminoacylation. In addition to its interaction with mitochondrial seryl-tRNA synthetase (SARS2), we further discovered an interaction between mitochondrial threonyl-tRNA synthetase (TARS2) and METTL8-Iso1. METTL8-Iso1 substantially stimulated the aminoacylation activities of SARS2 and TARS2 in vitro, suggesting a functional connection between mitochondrial tRNA modification and charging. Altogether, our results deepen the mechanistic insights into mitochondrial m3C32 biogenesis and provide a valuable route to prepare cytoplasmic/bacterial tRNAs with only a m3C32 moiety, aiding in future efforts to investigate its effects on tRNA structure and function.

A fungus (Trametes pubescens) resists cadmium toxicity by rewiring nitrogen metabolism and enhancing energy metabolism.

As a primary goal, cadmium (Cd) is a heavy metal pollutant that is readily adsorbed and retained in rice, and it becomes a serious threat to food safety and human health. Fungi have attracted interest for their ability to remove heavy metals from the environment, although the underlying mechanisms of how fungi defend against Cd toxicity are still unclear. In this study, a Cd-resistant fungus Trametes pubescens (T. pubescens) was investigated. Pot experiments of rice seedlings colonized with T. pubescens showed that their coculture could significantly enhance rice seedling growth and reduce Cd accumulation in rice tissues. Furthermore, integrated transcriptomic and metabolomic analyses were used to explore how T. pubescens would reprogram its metabolic network against reactive oxygen species (ROS) caused by Cd toxicity. Based on multi-omic data mining results, we postulated that under Cd stress, T. pubescens was able to upregulate both the mitogen-activated protein kinase (MAPK) and phosphatidylinositol signaling pathways, which enhanced the nitrogen flow from amino acids metabolism through glutaminolysis to α-ketoglutarate (α-KG), one of the entering points of tricarboxylic acid (TCA) cycle within mitochondria; it thus increased the production of energy equivalents, adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) for T. pubescens to resist oxidative damage. This study can enable a better understanding of the metabolic rewiring of T. pubescens under Cd stress, and it can also provide a promising potential to prevent the rice paddy fields from Cd toxicity and enhance food safety.

Potential Misidentification of Natural Isomers and Mass-Analogs of Modified Nucleosides by Liquid Chromatography-Triple Quadrupole Mass Spectrometry.

Triple quadrupole mass spectrometry coupled to liquid chromatography (LC-TQ-MS) can detect and quantify modified nucleosides present in various types of RNA, and is being used increasingly in epitranscriptomics. However, due to the low resolution of TQ-MS and the structural complexity of the many naturally modified nucleosides identified to date (>160), the discrimination of isomers and mass-analogs can be problematic and is often overlooked. This study analyzes 17 nucleoside standards by LC-TQ-MS with separation on three different analytical columns and discusses, with examples, three major causes of analyte misidentification: structural isomers, mass-analogs, and isotopic crosstalk. It is hoped that this overview and practical examples will help to strengthen the accuracy of the identification of modified nucleosides by LC-TQ-MS.

MicroRNA-21 Contributes to Cutaneous Squamous Cell Carcinoma Progression via Mediating TIMP3/PI3K/AKT Signaling Axis.

BACKGROUND: Though the therapeutic potentials of microRNAs (miRNAs) are extensively explored in cutaneous squamous cell carcinoma (CSCC), the concrete function of miR-21 in this disorder has not been thoroughly comprehended. Therein, this work is launched to clarify the miR-21-pivoted mechanism in CSCC from the perspective of tissue inhibitor of metalloproteinases-3 (TIMP3) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. METHODS: Microarray-based analysis was utilized to screen out miR-21 with the most up-regulated expression in CSCC tissues. The relation between miR-21 and TIMP3 expression in tissues, and the overall survival of CSCC patients was evaluated. Loss-of-function assays were performed in cells to explore the independent and combined functions of miR-21 and TIMP3 in CSCC cell progression. Mice were injected with miR-21 inhibitor or TIMP3 si for identifying their roles in tumor formation and liver metastasis. The mechanism among miR-21, TIMP3 and PI3K/AKT pathway was interpreted. RESULTS: MiR-21 was up-regulated while TIMP3 was down-regulated in CSCC tissues, which were connected with unsatisfactory survival of patients. Down-regulating miR-21 inhibited CSCC cell progression and retarded CSCC tumor formation and metastasis in mice. Silencing of TIMP3 reversed the effects of miR-21 down-regulation on CSCC progression. Besides, down-regulating miR-21 inhibited PI3K/AKT pathway activation in CSCC cells via mediating TIMP3. CONCLUSION: It is elucidated that miR-21 depletion impedes CSCC cell invasion and metastasis via enhancing TIMP3 and suppressing PI3K/AKT pathway activation.

Anti-oxidative effect of zinc in human umbilical cord mesenchymal stem cells.

Human umbilical cord mesenchymal stem cells (HUC-MSCs) are pluripotent and functional in many biological processes, by which releasing secretary factors to promote the self-repairing of damaged tissue or developing into functional cell at local organ. However, there is a high risk that oxidative stress would reduce the pluripotency and factor-secretion during the preparation and transplantation. Therefore, reducing oxidative stress is expected to improve the efficacy of HUC-MSCs therapy. Zinc (Zn) is an essential trace element which involves in the resistance of oxidative stress. To investigate Zn-regulated signaling pathways, we have profiled the gene expression at transcriptome level in primary HUC-MSCs treated with zinc sulfate, followed with GO and KEGG gene enrichment analysis. Zn treatment improved signal pathways for mineral absorption, cell growth, and cell death. Zn deficiency was mimicked by TPEN administration, which suppressed cell proliferation and reduced the expression of HUC-MSCs surface stem cell markers CD73, CD90 and CD105 by flow cytometry. Nuclear factor erythrocyte 2 related factor 2 (Nrf2) plays an important role in antioxidant biological processes. In vitro treatment of Zn significantly increased Nrf2 and Sirt3 expression at gene level and protein level respectively. Zn supplementation inhibited TPEN-induced failure of cell survival and reversed the reduction of Nrf2 and Sirt3 expression, which further reduced the production of ROS. Zn successfully presented its anti-oxidation effect by activating Nrf2/Sirt3 signaling pathway in HUC-MSCs. Zn supplementation may improve the efficacy of HUC-MSCs therapy with reduced oxidative stress.

Acitretin induces apoptosis through CD95 signalling pathway in human cutaneous squamous cell carcinoma cell line SCL-1.

Skin cancers are by far the most common human malignancies. Retinoids have shown promising preventive and therapeutic effects against a variety of human malignancies. The aim of this study was to investigate the apoptosis-inducing effect of acitretin on human skin squamous cell carcinoma (SCC) SCL-1 cells. We found that acitretin preferentially inhibited the growth of SCL-1 cells in a dose- and time-dependent manner, but not of non-malignant keratinocyte HaCaT cells. This inhibition appeared to be due to induction of apoptosis as revealed by enzyme-linked immunosorbent assay. AnnexinV/propidium iodide assay and morphological observation confirmed the pro-apoptotic effect of acitretin on SCL-1 cells. We further demonstrated that apoptosis was induced within 1-2 days and involved activation of caspases-8, -9, -3 and poly (ADP-ribose) polymerase (PARP). Caspase-8 inhibitor effectively suppressed acitretin-induced apoptosis whereas caspase-9 inhibitor did not. Acitretin increased the levels of CD95 (Fas), CD95-ligand and Fas-associated death domain. Neutralizing ZB4 anti-Fas antibody significantly inhibited the apoptosis in SCL-1 cells induced by acitretin. These results suggest that acitretin is able to induce apoptosis in skin cancer cells possibly via death receptor CD95 apoptosis pathway without affecting the viability of normal keratinocyte.

Liquid Chromatography/Mass Spectrometry based serum metabolomics study on recurrent abortion women with antiphospholipid syndrome.

OBJECTIVE: The antiphospholipid syndrome (APS) is an important cause of acquired thromboembolic complications and pregnancy morbidity. The pathogenic mechanisms that damage the fetal-maternal unit and cause abnormal placental development are incompletely understood in APS patients. Liquid Chromatography/Mass Spectrometry (LC/MS) based metabolomics are applied for the mechanism of disease and further supporting the research of diagnosis and management in recent years. The aim of this research was to investigate the difference of serum metabolic profiles in recurrent abortion women with APS and healthy women to explore the mechanism of this disease. METHODS: Serum samples of 25 recurrent abortion women with APS and 25 healthy women were collected and analyzed by LC/MS in this study. Potential biomarkers were discovered by multivariate statistical analysis and then identified based on analysis results. RESULTS: Totally, we identified five biomarkers that involved in different metabolic pathway such as purine metabolism, amino acid metabolism and tyrosine metabolism. These biomarkers showed different roles in disease development. CONCLUSION: Metabolomics was proved as a powerful tool in understanding the mechanism of recurrent abortion caused by APS.